The primary goal of the Cancer Gene Discovery and Cancer Biology Postdoctoral Research Training Program at Cold Spring Harbor Laboratory (CSHL) is to prepare the next generation of cancer biologists to pursue independent research that integrates cancer gene discovery with functional biology in order to facilitate the development of novel cancer therapeutic, diagnostic and/or preventive strategies. Features of the three year research training program include a combination of: mandatory and elective didactic components; structured career development guidance; monthly research seminars; graduate and community based teaching opportunities; and research experiences in laboratories affiliated with the CSHL National Cancer Institute (NCI) designated Cancer Center. Postdoctoral trainees benefit from a small faculty to trainee ratio in nineteen potential preceptor laboratories, an on-site internationally renowned Scientific Meetings and Courses program, and newly expanded state-of-the-art cancer research facilities. Cancer research opportunities span three highly integrated areas that are augmented and supported by a growing Quantitative Biology program with dedicated faculty and resources. The cancer research areas include; 1) Cancer Gene Discovery - sequencing, genetic models, chromosome engineering; 2) Cancer Gene Function - splicing, replication, epigenetics, nuclear structure, tumor growth and metastasis; and 3) Human Cancer Impact - drug sensitivity and resistance, clinical correlates, disease status and outcomes. CSHL is seeking National Research Service Award Institutional Training grant support from the NCI for 5 positions in the first year, and 6 in each of the following four years. The training program benefits from a collaborative and multidisciplinary research environment, an internal Executive Committee that includes trainee participation, and an independent External Advisory Committee. Trainees gain an in-depth and integrated understanding of cancer genetics and its impact on biological processes relevant to human malignancy, and will be prepared to pursue independent cancer research careers upon completion of the program. Points raised by the previous review panel have been carefully considered and are addressed in this revised application.